Li Yuqi, Wang Juan, Zhou Tao, Liu Zhiyu, Meng Chunyang, Deng Qingfu
Department of Urology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China.
Department of Urology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China.
Reprod Toxicol. 2025 Jul 12;137:108999. doi: 10.1016/j.reprotox.2025.108999.
In recent years, antidiabetic drugs have been increasingly repurposed for conditions beyond diabetes. However, their effects on erectile dysfunction (ED) remain inadequately understood. This study utilizes Mendelian randomization (MR) analysis to investigate the potential impact of antidiabetic drug targets on the risk of ED.
We retrieved target gene information for eight classes of antidiabetic drugs from the DrugBank and GeneCards databases and subsequently identified instrumental variables for the corresponding genes using data from the eQTLGen consortium. Following data integration, we conducted MR, meta-analysis, and summary-data-based mendelian randomization (SMR) to systematically investigate the potential causal relationship between antidiabetic drug target genes and ED. Furthermore, we performed sensitivity analyses to assess the robustness and reliability of the observed associations.
This study investigated the potential association between 24 antidiabetic drug target genes and ED, identifying 11 positive target genes and included in subsequent analyses. Using MR, meta-analysis, and summary-data-based MR, we observed a significant negative correlation between IGF1R and ED (OR 0.907, 95 % CI 0.859-0.959, P < 0.001). These findings suggest that IGF1R may exert a protective effect against ED, offering novel theoretical support for the potential repurposing of antidiabetic drugs in ED treatment.
Our findings indicate that elevated expression of IGF1R may be associated with a reduced risk of erectile dysfunction (ED). This observation implies that the rational application of insulin and its analogs could confer potential preventive benefits against ED, offering novel theoretical insights for the development of targeted therapeutic strategies.
近年来，抗糖尿病药物越来越多地被用于治疗糖尿病以外的疾病。然而，它们对勃起功能障碍（ED）的影响仍未得到充分了解。本研究利用孟德尔随机化（MR）分析来探究抗糖尿病药物靶点对ED风险的潜在影响。
我们从DrugBank和GeneCards数据库中检索了八类抗糖尿病药物的靶基因信息，随后使用eQTLGen联盟的数据为相应基因确定工具变量。在数据整合之后，我们进行了MR、荟萃分析和基于汇总数据的孟德尔随机化（SMR），以系统地研究抗糖尿病药物靶基因与ED之间的潜在因果关系。此外，我们进行了敏感性分析，以评估观察到的关联的稳健性和可靠性。
本研究调查了24个抗糖尿病药物靶基因与ED之间的潜在关联，确定了11个阳性靶基因并纳入后续分析。使用MR、荟萃分析和基于汇总数据的MR，我们观察到IGF1R与ED之间存在显著负相关（OR 0.907，95%CI为0.859 - 0.959，P < 0.001）。这些发现表明，IGF1R可能对ED具有保护作用，为抗糖尿病药物在ED治疗中的潜在重新利用提供了新的理论支持。
我们的研究结果表明，IGF1R表达升高可能与勃起功能障碍（ED）风险降低有关。这一观察结果意味着合理应用胰岛素及其类似物可能对ED具有潜在的预防益处，为制定针对性治疗策略提供了新的理论见解。
